U.S. patent number 8,903,492 [Application Number 11/349,540] was granted by the patent office on 2014-12-02 for ion imbalance detector.
This patent grant is currently assigned to Medtronic, Inc.. The grantee listed for this patent is James K. Carney, Cygni Chan, Tara L. Nahey, Timothy H. Robinson, Orhan Soykan. Invention is credited to James K. Carney, Cygni Chan, Tara L. Nahey, Timothy H. Robinson, Orhan Soykan.
United States Patent |
8,903,492 |
Soykan , et al. |
December 2, 2014 |
Ion imbalance detector
Abstract
In general, the invention is directed to methods and devices for
determining an ion concentration in the extracellular fluid of a
patient. As examples, the ion may be one or more of potassium,
sodium, chloride, or calcium. A system includes an electrode
deployed in or near a tissue, such as a skeletal muscle, of the
patient. A pulse generator supplies one or more stimulations to the
tissue, and a sensor, such as an accelerometer, detects the
response of the tissue to the stimulations. A processor determines
a concentration of ions in the extracellular fluid as a function of
the response. The system may detect an ion imbalance based upon the
determined concentration of ions.
Inventors: |
Soykan; Orhan (Inver Grove
Heights, MN), Robinson; Timothy H. (Savage, MN), Carney;
James K. (Brooklyn Park, MN), Nahey; Tara L.
(Minneapolis, MN), Chan; Cygni (Shoreview, MN) |
Applicant: |
Name |
City |
State |
Country |
Type |
Soykan; Orhan
Robinson; Timothy H.
Carney; James K.
Nahey; Tara L.
Chan; Cygni |
Inver Grove Heights
Savage
Brooklyn Park
Minneapolis
Shoreview |
MN
MN
MN
MN
MN |
US
US
US
US
US |
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Assignee: |
Medtronic, Inc. (Minneapolis,
MN)
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Family
ID: |
36263838 |
Appl.
No.: |
11/349,540 |
Filed: |
February 7, 2006 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20060241709 A1 |
Oct 26, 2006 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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60650497 |
Feb 7, 2005 |
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Current U.S.
Class: |
607/22 |
Current CPC
Class: |
A61B
5/1107 (20130101); A61B 5/14546 (20130101); A61B
5/1451 (20130101); A61B 5/7278 (20130101); A61N
1/36135 (20130101); A61N 1/36557 (20130101); A61B
5/4519 (20130101); A61B 5/1473 (20130101); A61B
5/14542 (20130101); A61B 5/686 (20130101); A61M
5/14276 (20130101); A61M 5/1723 (20130101); A61B
2562/0219 (20130101); A61B 5/053 (20130101); A61N
1/36167 (20130101) |
Current International
Class: |
A61N
1/36 (20060101) |
Field of
Search: |
;607/22 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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0 906 768 |
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Feb 2004 |
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EP |
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0906768 |
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Feb 2004 |
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EP |
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2009026603 |
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Mar 2009 |
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WO |
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Other References
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Primary Examiner: Bertram; Eric D
Attorney, Agent or Firm: Hahn & Voight PLLC Hahn; Roger
C.
Parent Case Text
This application claims the benefit of U.S. provisional application
Ser. No. 60/650,497, filed Feb. 7, 2005, the entire content of
which is incorporated herein by reference.
This application is related to U.S. patent application Ser. No.
11/349,058, filed Feb. 7, 2006, entitled "Potassium Monitoring,"
the entire content of which is incorporated herein by reference.
Claims
The invention claimed is:
1. A system comprising: a pulse generator configured to generate an
electrical stimulation; an electrode configured to deliver the
electrical stimulation to a tissue in a patient; a sensor
configured to detect a mechanical response of the tissue to the
electrical stimulation; and a processor configured to determine a
concentration of ions in extracellular fluid of the patient as a
function of the response.
2. The system of claim 1, wherein the tissue is at least one of
skeletal muscle, smooth muscle, cardiac muscle, or skin.
3. The system of claim 1, wherein the ions are at least one of
potassium, sodium, chloride, calcium, or magnesium ions.
4. The system of claim 1, wherein the ions are at least one of
drugs, small molecules, or endogenously charged molecules.
5. The system of claim 1, wherein the processor is further
configured to determine a concentration of ions in the
extracellular fluid of the patient by at least one of determining
an absolute concentration of ions in the extracellular fluid,
determining a relative concentration of ions in the extracellular
fluid or determining a change in concentration of ions in the
extracellular fluid over time.
6. The system of claim 5, wherein the pulse generator is configured
to generate a set of electrical stimulations at a known
frequency.
7. The system of claim 5, wherein the processor is further
configured to control the timing of a set of electrical
stimulations generated by the pulse generator.
8. The system of claim 1, wherein the pulse generator is further
configured to generate a set of electrical stimulations.
9. The system of claim 1, wherein the processor is further
configured to determine a concentration of ions in the
extracellular fluid as a function of at least one of a sustained
contraction of the tissue, a rippled contraction of the tissue, a
rate of relaxation of the tissue, a pulse width of the response,
the occurrence of summation in the response or the amplitude of the
response.
10. The system of claim 1, wherein the electrode is a first
electrode, the system further comprising a housing and a second
electrode in the housing.
11. The system of claim 1, wherein the sensor comprises at least
one of an optical sensor, an accelerometer, a pressure sensor, or a
piezoelectric sensor.
12. The system of claim 1, wherein the processor is further
configured to control delivery of pacing therapy to a heart of the
patient.
13. The system of claim 1, further comprising a lead configured to
couple the electrode to the pulse generator.
14. The system of claim 1, wherein the system further comprises at
least one of a lead configured to deliver a pacing stimulation to a
heart, a lead configured to deliver a pacing stimulation to a
nerve, or a pump configured to deliver a drug from a reservoir.
15. The system of claim 1, wherein at least one of the pulse
generator, electrode, sensor and processor is configured to be
implanted in a human or animal body.
16. The system of claim 1, wherein the processor monitors the
concentration of ions to predict an arrhythmia.
17. A method comprising: delivering an electrical stimulation to a
tissue in a patient; detecting a response of the tissue to the
electrical stimulation; and determining a concentration of ions in
extracellular fluid of the patient as a function of the response,
wherein the tissue is at least one of skeletal muscle, smooth
muscle, cardiac muscle, nerve tissue, or skin.
18. The method of claim 17, wherein the ions are at least one of
potassium, sodium, chloride, calcium, or magnesium ions.
19. The method of claim 17, wherein the ions are at least one of
drugs, small molecules, or endogenously charged molecules.
20. The method of claim 17, wherein determining the concentration
of ions in the extracellular fluid of the patient comprises at
least one of determining an absolute concentration of ions in the
extracellular fluid, determining a relative concentration of ions
in the extracellular fluid, or determining a change in
concentration of ions in the extracellular fluid over time.
21. The method of claim 17, wherein determining the concentration
of ions in the extracellular fluid of the patient comprises at
least one of detecting a sustained contraction of the tissue,
detecting a rippled contraction of the tissue, detecting a rate of
relaxation of the tissue, detecting a pulse width of the response,
detecting the occurrence of summation in the response, or detecting
the amplitude of the response.
22. The method of claim 17, further comprising delivering a therapy
to the patient as a function of the response.
23. The method of claim 17, wherein the electrical stimulation is a
first electrical stimulation and the response is a first response,
the method further comprising: delivering a second electrical
stimulation to the tissue; detecting a second response of the
tissue to the second electrical stimulation; and determining a
change in concentration of ions in the extracellular fluid of the
patient as a function of the first and second responses.
24. The method of claim 17, further comprising: detecting a
triggering event; and delivering the electrical stimulation in
response to the triggering event.
25. The method of claim 17, further comprising: determining whether
conditions are suitable for determining the concentration of ions;
and delivering the electrical stimulation when the conditions are
suitable.
26. The method of claim 17, further comprising monitoring the
concentration of ions to predict an arrhythmia.
27. The method of claim 17, further comprising at least one of
recording information relating to the determination, or issuing a
warning to at least one of the patient or a caregiver based upon
the determination.
28. The method of claim 17, further comprising transmitting
information relating to the determination to another device.
29. A non-transitory computer-readable medium comprising
instructions that cause a programmable processor to: control a
pulse generator to deliver an electrical stimulation to a tissue in
a patient; receive from a sensor a signal indicative of a
mechanical response of the tissue to the electrical stimulation;
and determine a concentration of ions in extracellular fluid of the
patient as a function of the response.
30. The medium of claim 29, wherein the tissue is at least one of
skeletal muscle, smooth muscle, or skin.
31. The medium of claim 29, wherein the ions are at least one of
potassium, sodium, chloride, calcium, or magnesium ions.
32. The medium of claim 29, wherein the ions are at least one of
drugs, small molecules, or endogenously charged molecules.
33. The medium of claim 29, the instructions further causing the
processor to determine the concentration of ions in the
extracellular fluid by determining a change in concentration of
ions in the extracellular fluid over time.
34. The medium of claim 29, the instructions further causing the
processor to determine the concentration of ions in the
extracellular fluid by at least one of detecting a sustained
contraction of the tissue, detecting a rippled contraction of the
tissue, detecting a rate of relaxation of the muscle, detecting a
pulse width of the response, detecting the occurrence of summation
in the response, or detecting the amplitude of the response.
35. The medium of claim 29, the instructions further causing the
processor to control delivery of a therapy to the patient as a
function of the response.
36. The medium of claim 29, further comprising instructions that
cause the programmable processor to monitor the concentration of
ions to predict an arrhythmia.
37. A system comprising: means for delivering an electrical
stimulation to a tissue in a patient; means for detecting a
response of the tissue to the electrical stimulation; and means for
determining a concentration of ions in extracellular fluid of the
patient as a function of the response, wherein the tissue comprises
at least one of skeletal muscle, smooth muscle, cardiac muscle,
nerve tissue, and skin.
38. The system of claim 37, further comprising means for delivering
therapy to the patient as a function of the response.
39. The system of claim 37, further comprising means for monitoring
the concentration of ions to predict an arrhythmia.
40. A method comprising: delivering an electrical stimulation to a
tissue in a patient; detecting a mechanical response of the tissue
to the electrical stimulation; and determining a concentration of
ions in extracellular fluid of the patient as a function of the
response.
Description
TECHNICAL FIELD
The invention relates to systems and methods associated with
monitoring physiological conditions, and in particular, to systems
and methods associated with monitoring concentrations of ions in
extracellular fluid.
BACKGROUND
The concentration of ions, such as potassium, sodium, chloride, and
calcium, in the extracellular fluid (ECF) of a patient is of
clinical significance. Abnormal ion concentration levels in the ECF
can be a product of the pharmacological management of patients with
heart failure. In general, the concentration of potassium and
calcium ions in the intracellular fluid (ICF) of cardiac muscle or
other tissue is high in comparison to potassium and calcium ions in
the ECF. In contrast, the concentration of chloride and sodium ions
is greater in the ICF than the ECF. As an example, elevated
potassium ion concentration, denoted [K.sup.+], in the ECF causes a
reduced concentration gradient between ICF and ECF. A reduction of
the resting membrane potential is associated with the reduction in
the concentration gradient, often resulting in ectopic foci and
arrhythmia.
A reduction in concentration gradient further affects the magnitude
and duration of the action potential. The change in membrane
potential caused by an action potential, which is about 120 mV in
healthy cardiac muscle, can be reduced substantially. In addition,
the duration of the action potential, which is about 250
milliseconds in healthy cardiac tissue, can be diminished.
The concentration of ions may have additional clinical significance
as well, and for some patients the certain ion concentrations may
be an important factor worth monitoring. For example, trauma
patients, burn patients, diabetic patients with ketoacidosis, renal
patients on dialysis, patients experiencing pulmonary edema, and
cardiac arrest patients may have electrolyte fluctuations,
particularly fluctuations of potassium ion concentrations. In
addition, potassium ion retention accompanies the onset of some
medical conditions, such as Addison's disease.
SUMMARY
In general, the invention is directed to methods and devices for
determining a concentration of one or more ions in extracellular
fluid of a patient. As examples, the ion may be any of potassium,
sodium, chloride, or calcium. Further, as other examples, the ions
may be drugs that result in ions in the blood or extracellular
fluid, small molecules, or endogeounously charged molecules. A
system includes electrodes, and at least one of the electrodes is
deployed in or near a tissue of the patient. The tissue may be a
skeletal muscle, such as the pectoral muscle. A pulse generator
supplies one or more stimulations to the tissue, and a sensor
detects the response of the tissue to the stimulations. A processor
determines a concentration of potassium ion as a function of the
response.
As used herein, determining a concentration of ions in
extracellular fluid of the patient includes, but is not limited to,
determining an absolute concentration, such as measuring or
estimating a molarity. Determining a concentration of ions can also
includes determining a relative concentration, such as a
concentration with respect to a baseline. Furthermore, determining
a concentration of ions can include determining a change in
concentration over time. In any case, the system may detect an ion
imbalance in a patient.
The invention can be implemented as a stand-alone ion imbalance
detection system. The invention can also be implemented in
conjunction with an implantable medical device such as a cardiac
pacemaker, cardioverter-defibrillator, patient monitor, drug pump
or neurostimulator. The invention can be implemented as an external
system or a system having external and implantable elements.
In one embodiment, the invention presents a system comprising a
pulse generator configured to generate an electrical stimulation,
an electrode configured to deliver the electrical stimulation to a
tissue, such as a skeletal muscle, in a patient. The system further
includes a sensor configured to detect at least one response of the
tissue to the electrical stimulation, and a processor configured to
determine a concentration of ions in extracellular fluid of the
patient as a function of the response. The processor can be
configured to determine a concentration of ions as a function of a
sustained contraction of the tissue, for example, or a rippled
contraction of the tissue, a rate of relaxation of the tissue, a
pulse width of the response, the occurrence of summation in the
response or the amplitude of the response. The system can be
external, partially implantable or fully implantable.
In another embodiment, the invention is directed to a method that
includes delivering an electrical stimulation to a tissue in a
patient, detecting a response of the tissue to the electrical
stimulation, and determining a concentration of ions in
extracellular fluid of the patient as a function of the response.
The method can further include delivering a therapy to the patient
as a function of the response.
In a further embodiment, the invention is directed to a method
comprising delivering an electrical stimulation to a tissue in a
patient, detecting at least one response of the tissue to the
electrical stimulations and storing a relationship between a
concentration of ions in extracellular fluid of the patient and the
response. This method is useful for calibrating an ion imbalance
detection system according to the invention.
Additional embodiments of the invention include computer-readable
media comprising instructions that cause a programmable processor
to carry out any of the methods of the invention.
The invention may result in one or more advantages. Compared to
conventional techniques for detecting ion concentrations, the
invention offers convenience and supports long-term implantation.
Tests that rely upon laboratory analysis of blood samples require
that blood be drawn from the patient, and may not be available
outside a hospital setting. Electrochemistry-based ion sensors,
such as sensors for potassium, are implantable. However, these ion
sensors have not proven to be stable over long periods, and their
performance degrades over time. Optical sensors for ion
concentrations typically call for periodic replacement of
components, such as a disposable strip used for making
measurements. By contrast, the invention can be implanted, can
conveniently monitor ion concentrations, and can remain reliable
for extended periods of time.
In addition, the invention can be implemented within an IMD that
delivers therapy, such as a pacemaker or drug pump, or supports
other monitoring functions. Many patients experiencing heart
failure, for example, can benefit from the implantation of an IMD
that can monitor ion concentrations and apply one or more pacing
therapies. The invention can offer the further advantage of
implementation with one or more external elements, which can be
deployed without surgery.
The details of one or more embodiments of the invention are set
forth in the accompanying drawings and the description below. Other
features, objects, and advantages of the invention will be apparent
from the description and drawings, and from the claims.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1A is a schematic illustration of a human heart in conjunction
with an exemplary implantable medical device and an exemplary
electrode element according to an embodiment of the invention.
FIGS. 1B through 1E are schematic illustrations of an implantable
medical device with alternate embodiments of electrode
elements.
FIG. 1F is a schematic illustration of an exemplary external
medical device and an exemplary electrode element according to an
embodiment of the invention.
FIG. 2 is a schematic illustration of an implantation of an
exemplary implantable medical device and an exemplary electrode
element proximate to skeletal muscle.
FIG. 3 is a block diagram showing a system that can deliver one or
more electrical stimuli to a tissue and determine a concentration
of ions in extracellular fluid as a function of the response to the
stimuli.
FIGS. 4A and 4B are timing diagrams illustrating stimuli and the
responses of skeletal muscle thereto, according to various
embodiments of the invention.
FIG. 5 is a flow diagram illustrating a technique for calibrating a
medical device to determine a concentration of ions in
extracellular fluid.
FIG. 6 is a flow diagram illustrating a technique for monitoring
ion concentrations in extracellular fluid.
FIG. 7 is a schematic diagram of an experimental setup to test
muscle contractions due to electrical stimuli.
FIG. 8 is a graph of exemplary data showing muscle force in various
solutions of potassium versus time.
FIG. 9 is a graph of exemplary data showing contraction amplitude
versus potassium concentration.
DETAILED DESCRIPTION
FIG. 1A is a schematic illustration of an exemplary embodiment of a
system 10 that includes an implantable medical device (IMD) 12 in
relationship to a heart 14 of a patient. IMD 12 is configured to be
implanted in a human or animal body. As depicted in FIG. 1A, IMD 12
comprises a multi-chamber pacemaker having cardioversion and
defibrillation capabilities. Although it can be advantageous to
implement the invention with a multi-chamber pacemaker, the
invention is not limited to the particular IMD shown. Furthermore,
as discussed below, the invention need not be implemented as an
implantable medical device. The invention can be implemented as a
stand-alone ion monitor system, or in conjunction with a different
type of implantable or external device such as a patient monitor,
drug pump, muscle stimulator or neurostimulator. The ion whose
concentration is monitored may be any one of potassium (K.sup.+),
sodium (Na.sup.+), chloride (Cl.sup.-), or calcium (Ca.sup.2+).
Other ions may include magnesium (Mg.sup.2+), bicarbonate
(HCO.sub.3.sup.-), or any other ions found in intracellular fluid
(ICF) or extracellular fluid (ECF). Further, other ions may include
drugs that result in ions in the blood or extracellular fluid,
small molecules, or endogeounously charged molecules.
A right ventricular lead 16 includes an elongated insulative lead
body carrying one or more concentric coiled conductors separated
from one another by tubular insulative sheaths. The distal end of
right ventricular lead 16 is deployed in the right ventricle 18 of
heart 14. Located adjacent the distal end of the lead body are one
or more pace/sense electrodes 20, which are configured to deliver
cardiac pacing and are further configured to sense depolarizations
of right ventricle 18. A fixation mechanism 22 such as tines or a
screw-in element, anchors the distal end in right ventricle 18. The
distal end also includes an elongated coil electrode 24 configured
to apply cardioversion or defibrillation therapy. Each of the
electrodes is coupled to one of the coiled conductors within the
lead body. At the proximal end of right ventricular lead 16 is a
connector 26, which couples the coiled conductors in the lead body
to IMD 12 via a connector module 28.
A right atrial lead 30 includes an elongated insulative lead body
carrying one or more concentric coiled conductors separated from
one another by tubular insulative sheaths corresponding to the
structure of right ventricular lead 16. Located adjacent the
J-shaped distal end of right atrial lead 30 are one or more
pace/sense electrodes 32, which are configured to sense
depolarizations of and deliver pacing stimulations to right atrium
34. As shown in FIG. 1A, an elongated coil electrode 36 is provided
proximate to the distal end of right atrial lead 30, and is located
in right atrium 34 and the superior vena cava 38. At the proximal
end of the lead is a connector 40, which couples the coiled
conductors in right atrial lead 30 to IMD 12 via connector module
28.
A coronary sinus lead 42 includes an elongated insulative lead body
deployed in the great cardiac vein 44. The lead body carries one or
more coiled conductors coupled to one or more pace/sense electrodes
46. Electrodes 46 are configured to deliver ventricular pacing to
left ventricle 48 and are further configured to sense
depolarizations of left ventricle 48. Additional pace/sense
electrodes (not shown) may be deployed on coronary sinus lead 42
that are configured to pace and sense depolarizations of the left
atrium 50. At the proximal end of coronary sinus lead 42 is
connector 52, which couples the coiled conductors in coronary sinus
lead 42 to connector module 28.
An exemplary electrode element 54A is coupled to the distal end of
a lead 56. Lead 56 carries one or more conductors separated from
one another by insulative sheaths. A connector 58 at the proximal
end of the lead couples the conductors in lead 56 to IMD 12 via
connector module 28.
In addition to connector module 28, IMD 12 comprises a housing 60
formed from one or more materials, including conductive materials
such as stainless steel or titanium. Housing 60 may include
insulation, such as a coating of parylene or silicone rubber, and
in some variations, all or a portion of housing 60 may be left
uninsulated. The uninsulated portion of housing 60 can serve as a
subcutaneous electrode and a return current path for electrical
stimulations applied via other electrodes.
In the embodiment shown in FIG. 1A, electrode element 54A includes
two electrodes 62A and 62B. At least one of electrodes 62A and 62B
is deployed in or near test tissue and delivers stimulation to the
tissue, while the other provides a return current path. In the
embodiment shown in FIG. 1A, electrodes 62A and 62B are button
electrodes, but the invention encompasses other electrode types as
well. The invention will be described in terms of stimulation of
muscle cells, but the invention can encompass other test tissues as
well. The test tissue can comprise a collection of autologous or
non-autologous cells that are sensitive to the concentration of the
selected ion. For example, the test tissue may be one of cardiac
muscle, skeletal muscle, smooth muscle, nerve tissue, skin, or the
like. The ions may be one of K.sup.+, Na.sup.+, Cl.sup.-,
Ca.sup.2+, Mg.sup.2+, or HCO.sub.3.sup.-. Additionally, possible
ions may include drugs (such as Digitalis) that become ions in the
blood or ECF, small molecules, endogenously charged molecules, or
other molecules in their ionic forms. Concentrations of ions will
be depicted with brackets such as [K.sup.+], as in the example of
the concentration of potassium ions. While [K.sup.+] is discussed
in detail as an exemplary ion concentration herein, any other ion
concentrations may be additionally or alternatively detected
according to the invention.
As described below, IMD 12 includes one or more implantable pulse
generators (IPGs) (not shown in FIG. 1A) configured to generate
stimuli to be delivered to one or more muscles of the patient via
electrode element 54A. As described below, skeletal muscle is
generally the most desirable tissue, because it is usually readily
accessible and response of skeletal muscle can be readily related
to ion concentration. Furthermore, it may be desirable to stimulate
skeletal muscles that do not get much use and are less prone to
fatigue. The invention encompasses embodiments in which stimulation
and response of other kinds of tissue can be related to ion
concentration, but muscle tissue, such as skeletal muscle tissue is
the exemplary tissue described herein.
Further, as discussed above, the invention encompasses monitoring
other ion concentrations instead of or in addition to [K.sup.+].
For example, [Na.sup.+] or [Cl.sup.-] may be detected when
monitoring skeletal muscle due to the large concentration gradient
between the ICF and ECF. The invention encompasses monitoring the
concentration of any ion in the ECF or ICF based on the electrical
and/or mechanical response of any tissue to a stimulus.
Housing 60 may include one or more sensors (not shown in FIG. 1A)
configured to detect at least one response of the stimulated muscle
to the electrical stimulation or stimulations. In some embodiments,
the sensor may be deployed elsewhere, such as on the distal end of
lead 56. In general, the sensor detects the electromechanical
response of the stimulated muscle. Examples of sensors will be
described below.
In general, the distance between electrodes 62A and 62B can be a
function of the pulse magnitude generated by an IPG, a target
stimulation magnitude, and the kind of electrodes employed. For
example, to deliver a stimulus with a field strength of 10 volts
per centimeter (V/cm) using IMD 12 which is capable of producing 2
V pulses, electrodes 62A and 62B can be separated by two
millimeters. The invention is not limited to any particular
physical dimensions or stimulation magnitudes, however.
IMD 12 also includes one or more IPGs configured to generate pacing
stimuli to be delivered to one or more chambers of heart 14. The
IPGs that stimulate heart 14 may be, but need not be, the same IPG
that generates muscle stimulations. IMD 12 further includes one or
more processors (not shown in FIG. 1A) that regulate the delivery
of pacing pulses. The processor in IMD 12 is configured to apply a
variety of pacing modes, including therapies that may be beneficial
for patients suffering from heart failure, such as cardiac
potentiation therapy (CPT) or cardiac resynchronization therapy
(CRT). CPT generally involves electrically stimulating one or more
heart chambers to induce post-extrasystolic potentiation, and CRT
involves delivering pacing pulses to one or both ventricles to
synchronize ventricular contractions.
FIG. 1B is a schematic illustration of IMD 12, with an alternate
embodiment of an electrode element 54B. In the embodiment depicted
in FIG. 1B, electrode element 54B, like electrode element 54A, is
coupled to the distal end of lead 56, which carries one or more
conductors separated from one another by insulative sheaths and is
coupled to connector module 28 via connector 58. Electrode element
54B includes two electrodes 62C and 62D, which deliver electrical
stimulation to muscle, or other tissue sensitive to [K.sup.+], and
provide a return current path. In other embodiments, electrodes 62C
and 62D may deliver electrical stimulation to the same tissue or
another tissue sensitive to a different ion concentration, such as
[Na.sup.+] or [Cl.sup.-].
Electrode element 54B resembles a pace/sense electrode, such as
pace/sense electrode 32 in FIG. 1A, in that electrode element 54B
includes a tip electrode 62C and a ring electrode 62D. Dimensions
of electrode element 54B may be comparable to those of conventional
pace/sense electrodes. Although not shown in FIG. 1B, the distal
end of lead 56 may include one or more fixation mechanisms
configured to prevent or reduce lead migration.
FIG. 1C is a schematic illustration of IMD 12, with another
alternate embodiment of an electrode element 54C. In the embodiment
depicted in FIG. 1C, electrode element 54C includes an electrode
62E deployed at the distal end of lead 56, and another electrode
62F in the body of housing 60. Housing electrode 62F can be
deployed at any site in housing 60. Lead electrode 62E is
configured to generate an intense electrical field at the site of
stimulation. A point at the distal end of lead electrode 62E causes
the electric field to be more intense at the point, which can
improve the likelihood of stimulation of muscle tissue or other
tissue sensitive to the concentration of an ion of interest, such
as [K.sup.+]. The distal end of lead 56 may include one or more
fixation mechanisms configured to prevent or reduce lead
migration.
FIG. 1D is a schematic illustration of IMD 12, with an additional
alternate embodiment of an electrode element 54D. Electrode element
54D includes an electrode 62G deployed on a fixed mount 64. In the
embodiment depicted in FIG. 1D, fixed mount 64 is coupled to
connector module 28, but fixed mount 64 may also be deployed
elsewhere on IMD 12. Exemplary electrode 62G, like electrode 62E in
FIG. 1C, is configured to generate an intense electrical field at
the site of stimulation. Another electrode 62H is deployed in the
body of housing 60.
As discussed below, some implantations if IMD 12 may place IMD 12
in direct contact with muscle such as skeletal muscle. The
embodiment depicted in FIG. 1D may be desirable in such
implantations, as electrodes 62G and 62H can be deployed without
leads.
FIG. 1E is a schematic illustration of IMD 12, with a further
alternate embodiment of an electrode element 54E. Electrode element
54E includes two electrodes 62I and 62J deployed in housing 60. In
a variation of this embodiment, housing 60 may include an array of
three or more electrodes. As with the embodiment shown in FIG. 1D,
the embodiment shown in FIG. 1E may be desirable in implantations
in which IMD 12 is implanted in direct contact with muscle or other
ion concentration sensitive tissue.
FIG. 1F is a schematic illustration of a further embodiment of the
invention, in which one or more elements are external and are not
configured to be implantable in a human or animal body. In the
embodiment depicted in FIG. 1F, external medical device 65 includes
one or more IPGs (not shown in FIG. 1F) configured to generate
stimuli to be delivered to one or more muscles of the patient via
electrode element 66. Examples of medical devices that can be
configured to generate stimuli to be delivered to muscles via an
electrode element are a Transcutaneous Electrical Nerve Stimulation
(TENS) unit, an Electronic Muscle Stimulation (EMS) unit and an
electro-acupuncture unit. The invention is not limited to such
medical devices, however. Medical device 65 or electrode element 66
may also include one or more sensors (not shown in FIG. 1F)
configured to detect an electromechanical response of the
stimulated muscle to the electrical stimulation or stimulations. In
a variation, a sensor module distinct from device 65 or electrode
element 66 may be deployed on the patient's skin to detect the
electromechanical response.
Electrode element 66 is coupled to medical device 65 via lead 67.
Electrode element 66 includes two electrodes 68A and 68B, which
deliver electrical stimulation to muscle, or other tissue sensitive
to [K.sup.+] or another ion concentration, and provide a return
current path. In the example of FIG. 1F, electrodes 68A and 68B are
deployed externally with adhesive pads 69A and 69B, which adhere to
the skin. Electrodes 68A and 68B may deliver an electrical
stimulation to any of several tissues, especially skeletal muscles
located beneath the skin. Although the embodiment shown in FIG. 1F
is completely external with no implantable elements, the invention
encompasses embodiments that have external and implantable
elements.
The invention is not limited to the particular embodiments depicted
in FIGS. 1A through 1F. For purposes of discussing the invention
and its operation, the description below will focus principally
upon implantable embodiments, and in particular, the embodiment
depicted in FIG. 1A. Further, as discussed above, the invention is
not limited to stimulation of skeletal muscle tissue, or
stimulation via leads or electrodes that are separate from the
leads or electrodes used to deliver therapeutic stimulation. In
other words, ion imbalance may be determined directly in the organ
of interest without the use of an additional stimulation pulse or
stimulation lead. For example, in some embodiments, ion imbalance
may be monitored by detecting the response of cardiac muscle to the
therapeutic pacing stimuli delivered to heart 14. Further, CPT may
be used to determine an ion concentration. CPT therapy provides an
additional stimulus near the time of the T wave of the cardiac
electrical signal to create a stronger ventricular contraction of
heart 14. The response to the stimulus may be sensitive to
[Ca.sup.2+], but other ion concentrations may be determined as
well.
FIG. 2 is a schematic illustration of an exemplary implantation in
a patient 70 of the apparatus depicted in FIG. 1A. Right
ventricular lead 16, right atrial lead 30 and coronary sinus lead
42 are deployed in heart 14 via access through a vein such as the
subclavian vein (not shown). Electrode element 54A and lead 56, by
contrast, do not enter the cardiovascular system.
Rather, electrode element 54A is deployed proximate to skeletal
muscle. In the exemplary implantation depicted in FIG. 2, electrode
element 54A is deployed proximate to the sternal portion 72 and
clavicular portion 74 of the Pectoralis major. The invention also
supports implantations in which electrode element 54A is deployed
proximate to other skeletal muscles, other muscles, or other
tissues sensitive to [K.sup.+], [Na.sup.+], [Cl.sup.-],
[Ca.sup.2+], [Mg.sup.2+], [HCO.sub.3.sup.-], or other ions in the
ECF. When a surgeon implants IMD 12 in a pocket, such as a pocket
proximate to the Pectoralis major according to a conventional
implantation procedure, the surgeon can deploy electrode element
54A proximate to a desired skeletal muscle. Electrode element 54A
may include a fixation mechanism such as a loop or Dacron mesh that
allows the surgeon to anchor electrode element 54A in place with
suture.
As shown in FIG. 2, housing 60 of IMD 12 is deployed in contact
with pectoral muscles 72 and 74. A conventional implantation
technique for some implantable devices, such as a pacemaker,
provides for deploying IMD 12 in direct contact with pectoral
muscle. In such implantations, embodiments such as those depicted
in FIGS. 1D and 1E may be feasible.
FIG. 3 is a block diagram illustrating components of an exemplary
system 10 such as the system depicted in FIG. 1A. Electrode element
54A includes electrodes 62A and 62B, which are configured to
deliver one or more electrical stimulations to a muscle or other
tissue sensitive to [K+] or another ion concentration. In a typical
embodiment, one of electrodes 62A and 62B introduces a stimulation
from IMD 12 to a skeletal muscle, and the other of electrodes 62A
and 62B provides the return current path.
In the embodiment shown in FIG. 3, IMD 12 includes a sensor 80 that
detects the electromechanical response of the muscle to the
stimulations delivered by electrodes 62A and 62B. Sensor 80 can
detect the mechanical response, the electrical response, or both.
Examples of mechanical responses are muscle tension, muscle
strength, muscle density, muscle length and pressure generated by
the muscle. Sensor 80 can be deployed inside housing 60 of IMD 12
or outside housing 60. Sensors such as an optical sensor could be
configured to respond to one or more of these mechanical responses.
An accelerometer, which responds to muscle movement, is another
example of a sensor that can detect a mechanical response. In some
embodiments of IMD 12, an accelerometer may be provided inside
housing 60 to detect patient activity or posture. Such an
accelerometer could also detect a mechanical response of stimulated
muscle. In an external implementation such as that depicted in FIG.
1F, an accelerometer may be disposed in device 65, in electrode
element 66, or as a separate module deployed on the patient's skin.
Further examples of sensors that can detect a mechanical response
are a pressure sensor and a piezoelectric sensor.
Sensor 80 can also be configured to detect an electrical response.
In some embodiments of the invention, electrodes 62A and 62B not
only deliver electrical stimulations to the muscle, but also convey
the electrical response to sensor 80. An example of a sensor that
detects an electrical response is an impedance sensor.
A pulse generator 82 in IMD 12 generates the stimulations that are
delivered to the skeletal muscle via electrodes 62A and 62B. Pulse
generator 82 may be, but need not be, the same component that
generates pacing stimulations that are delivered to heart 14. Pulse
generator 82 operates under the control of processor 84. Processor
84 can be embodied in one or more forms, such as a microprocessor,
digital signal processor, application specific integrated circuit
or full custom integrated circuit. In addition to controlling pulse
generator 82, processor 84 receives and analyzes signals detected
via sensor 80 that are indicative of the response of the muscle to
the stimulations, and determines a concentration of potassium or
other ions in extracellular fluid (ECF) of the patient as a
function of the signals. Therefore, processor 84 can detect an ion
imbalance in the patient. As discussed in more detail below,
[K.sup.+] in the ECF affects the response of the muscle or tissue
being monitored. In other embodiments, processor 84 may determine a
concentration of another ion, such as [Na.sup.+], [Cl.sup.-],
[Ca.sup.2+], [Mg.sup.2+], [HCO.sub.3.sup.-], a drug, small
molecule, or endogenously charged molecule. In the case of an ion
other than potassium, sensor 80 may be calibrated differently to
account for the detection of the selected ion concentration.
As used herein, determining a concentration of one or more ions in
ECF of the patient can include determining an absolute
concentration, such as measuring or estimating the molarity of
ions. Determining a concentration of potassium ions can also
include determining a relative concentration, such as a
concentration with respect to a baseline. Furthermore, determining
a concentration of potassium ions can include determining a change
in concentration over time. In practice, monitoring a change in
concentration over time has clear clinical advantages.
Processor 84 controls the scheduling of stimulations. Processor 84
may be configured to deliver the stimulations and monitor one or
more ion concentrations when the patient is in bed, for example.
Processor 84 may also be configured to deliver the stimulations and
monitor the ion concentration a predetermined number of times each
day.
Processor 84 may further be configured to determine whether
conditions are suitable for delivering stimulations and monitoring
the ion concentration. For example, it may be desirable to monitor
[K.sup.+] or other ion concentrations once a day when the patient
is inactive, particularly when the patient's muscles or other
tissues are relaxed and when there is less likelihood of extraneous
motion that could affect sensor 80. When the patient is physically
active, the physical activity can interfere with the monitoring of
ion concentrations, such as [K.sup.+]. Processor 84 may receive a
signal from sensor 80 or from another sensor that generates a
signal as a function of patient activity, such as an accelerometer.
On the basis of the signal, processor 84 may determine whether the
patient is too active or whether conditions are otherwise
unsuitable for monitoring. When processor 84 determines that
conditions are unsuitable, processor 84 may defer delivering
stimulations and may reschedule the stimulations for a later
time.
In addition, processor 84 may be programmed to deliver the
stimulations and monitor ion concentration in response to an event.
An exemplary event that could trigger delivery of stimulations and
monitoring of an ion concentration, such as [K.sup.+], is an
arrhythmia. When IMD 12 is a pacemaker or other device configured
to treat arrhythmia, IMD 12 may apply therapy to treat the
arrhythmia, then deliver the stimulations and monitor [K.sup.+], to
determine whether potassium ion concentration might be contributing
to the arrhythmia. Processor 84 can further be configured to
control delivery of pacing therapy to heart 14. Another exemplary
triggering event is the detection of a low level of physical
activity indicative of the onset of rest or sleep.
Alternatively, processor 84 may be programmed to deliver the
stimulations and monitor one or more ion concentrations, such as
[K.sup.+], to predict an arrhythmia based upon an ion imbalance. In
this manner, as an example, IMD 12 may detect poor regulation of
[K.sup.+] and allow a physician to modify patient medication or
suggest alternative diets. Exemplary medications may include
anti-arrhythmic drugs, potassium channel inhibitors, or diets that
include potassium sources such as bananas. In some embodiments, IMD
12 may notify the patient of an ion imbalance with an audible sound
or stimulation so that the patient may take precautions before the
arrhythmia.
In the embodiment depicted in FIG. 3, IMD 12 includes a memory
element 86 configured to store information about ion
concentrations. Memory element 86 can store information such as the
time when electrical stimulations were administered, the frequency
of the stimulations, the muscle's response to the stimulations, and
the determined ion concentration. Memory element 86 can also store
a history of such monitoring, and can store information concerning
the change in ion concentration over time.
In other embodiments, IMD 12 may detect more than one ion
concentration at one time in the form of individual concentrations
or concentration ratios. This multiple ion imbalance detection may
be performed with multiple sensors 80 or derived from the tissue
response. In any case, memory element 86 may store instructions for
processor 84 to perform the multiple ion imbalance detection and
store any data generated by the detection.
Further, memory element 86 may store instructions that cause a
programmable processor, such as processor 84, to carry out
techniques for monitoring potassium ion concentration. Memory
element 86 may include but is not limited to read-only memory,
random access memory, Flash memory, EPROM and a magnetic or optical
storage medium, or any combination thereof.
When processor 84 determines that an ion concentration or ion
imbalance is such that physiological functioning may be adversely
effected, or is otherwise a cause for concern, processor 84 may
take action. As an example, if the processor determines that
[K.sup.+] in ECF is elevated to the point that heart function may
be adversely affected, or when processor 84 determines that
[K.sup.+] in ECF is rising to a point of concern, the processor may
take action. Processor 84 may, for example, send a notification via
an input/output element 88. Input/output element 88 comprises one
or more elements that relay the message to the patient, the
patient's physician, or any other person or monitoring device.
Input/output element 88 can include, for example, a radio frequency
(RF) transmitter, an inductive coil transmitter or an audible
alarm. For example, input/output element 88 may issue a warning to
patient 12 if the determination of an ion concentration is above or
below a predetermined threshold.
Additionally, whether or not a determination that patient function
may be adversely affected has been made, input/output element 88
may transmit data stored by memory element 86, i.e. ion
concentration information or system 10 status data, to another
computing device such as a notebook computer, hand held computer,
physician programmer, personal computer, or network server. The
data may be transmitted for analysis and/or storage. In the case of
a network server, the data may be further forwarded to a hospital,
clinic, manufacturer of IMD 12, or another location where the data
may be analyzed or stored.
When processor 84 determines that ion concentration or imbalance in
ECF is of concern, processor 84 can also control the delivery of
therapy via a therapy element 90. Therapy element 90 can include,
for example, an implantable drug delivery device that delivers a
drug to the patient. The drug may be a diuretic, for example. As
the patient's body loses water due to increased urinary output, the
patient's arterial blood pressure declines, reducing the workload
of heart 14. In addition, increased urinary output enhances
elimination of K.sup.+ and other ions. Therapy element 90 can work
in concert with input/output element 88. For example, therapy
element 90 can administer a drug while input/output element 88 can
notify the patient that the patient should take an action, such as
contacting his physician or controlling the potassium in his
diet.
Therapy element 90 can also encompass elements that pace heart 14
via leads 16, 30 and 42, or any combination thereof, as depicted in
FIGS. 1A and 2. In general, however, pacing therapies would
probably not be applied to address or control [K.sup.+] or other
ion concentrations. Although pacing therapies such as cardiac
resynchronization and bi-ventricular pacing may be of benefit to
patients having heart failure, such pacing therapies would not
ordinarily be administered in response to elevated [K.sup.+]. Some
pacing therapies can cause [K.sup.+] to become even more elevated.
Accordingly, although it is unlikely that processor 84 would apply
pacing therapies to address elevated [K.sup.+], processor 84 may
monitor [K.sup.+] to determine whether such pacing therapies ought
to be employed or discontinued. In other words, processor 84 may
monitor [K.sup.+] or other ion concentrations to determine whether
pacing therapies are likely to be safe and effective.
FIGS. 4A and 4B are timing diagrams that illustrates exemplary
techniques by which processor 84 can determine a concentration of
potassium ion, as an example ion, in ECF as a function of the
response of skeletal muscle, as an example tissue, to stimulations
from an electrode element such as electrode elements 54A-E. Each
stimulus may have an amplitude of about two to twenty volts, for
example, and a pulse width of about 0.1 to 1.0 milliseconds.
Stimulus line 100 shows the timing of stimuli generated by pulse
generator 82 delivered to the skeletal muscle via electrodes such
as electrodes 62A-62J. Response line 104 depicts a response of
skeletal muscle to the stimulations in an environment where
[K.sup.+] is low relative to concentrations in ICF. In other words,
response line 104 depicts a response of skeletal muscle in a
"normal" patient. By contrast, response line 104 depicts a response
of skeletal muscle in a patient having elevated [K.sup.+]. A
patient having elevated [K.sup.+] is not normal and is at risk of
heart failure.
For purpose of illustration, the response is depicted as muscle
tension. Other responses, such as muscle motion or muscle length,
may also be evaluated, although the response waveforms may look
different from those in FIGS. 4A and 4B. In addition, the response
waveforms may look different from those in FIGS. 4A and 4B
depending upon the muscle or other tissue being stimulated. For
example, in embodiments that monitor the response of nervous tissue
to the stimulation as a means for monitoring ion concentration, the
response waveform may include one or more action potentials
Stimuli can be delivered in a range of frequencies, such as from
about 10 Hz to about 150 Hz. A first set of stimuli 106 at a low
frequency produces similar but distinct responses in normal
[K.sup.+] and elevated [K.sup.+] environments. Contractions 108 in
a normal muscle and contractions 110 in a muscle in an environment
of elevated [K.sup.+] are indicated by muscle tension as a function
of time. In comparison to one another, contractions 108 in a normal
muscle have a longer duration and may also exhibit some summation.
In the example of FIG. 4A, contractions 108 also exhibit a greater
amplitude. In contrast, contractions 110 in an elevated [K.sup.+]
environment are of a smaller amplitude, a shorter duration and
exhibit little or no summation.
A second set of stimuli 112 at a higher frequency produces distinct
responses in normal [K.sup.+] and elevated [K.sup.+] environments
as well. Contractions 114 in a normal muscle exhibit marked
summation. The muscle approaches tetanus, but, as depicted in FIG.
4, the frequency of stimulation is too low to produce a sustained
tetanic response. Instead, muscle contractions 114 exhibit
"ripples" or wavering, rather than the sustained contraction of
tetanus. In contrast with contractions 114, contractions 116 in an
elevated [K.sup.+] exhibit little or no summation.
A third set of stimuli 118 at an even higher frequency produces
contractions 120 in a normal muscle that show a tetanic response.
In particular, muscle tension rises steadily to a maximum and
levels off. Contractions 122 in an elevated [K.sup.+] environment,
by contrast, exhibit summation, but the rise in tension is rippled
and tension is not sustained. In other words, stimuli 118 produce a
sustained response 120 in a normal [K.sup.+] environment, but
produce a rippled response 122 in an elevated [K.sup.+]
environment.
The frequency of third set of stimuli 118 can be used to
distinguish a normal [K.sup.+] environment from an elevated
[K.sup.+] environment. The distinction can be achieved in a number
of ways. For example, an analog or digital highpass filter may be
employed to detect whether a ripple is present. Fourier or wavelet
analysis may be used to detect the presence of high frequency
components. Template matching or other morphological analysis may
be performed. Other forms of analog or digital signal analysis may
be used to detect the presence of a rippled response.
A fourth set of stimuli 124 at an even higher frequency produces
contractions 126 in a normal muscle and contractions 128 in an
elevated [K.sup.+] environment that are similar, in that both
exhibit a tetanic response. Consequently, stimuli at this frequency
would be less desirable for distinguishing a normal [K.sup.+]
environment from an elevated [K.sup.+] environment.
FIG. 4B shows additional distinction techniques. A set of stimuli
130 evokes responses 132, 134 similar to responses 120, 122 in FIG.
4A. In FIG. 4B, the quantity of interest is the decline of the
response following cessation of stimulation, which indicates how
fast the stimulated muscle relaxes. In FIG. 4B, the decline is
indicated by angles .alpha. and .beta. of lines tangent to the
responses. In general, the response returns to resting more quickly
in an elevated [K.sup.+] environment and more slowly in a normal
[K.sup.+] environment, so angle .beta. is generally larger and
indicative of a greater slope than angle .alpha.. Another
measurement of the decline of the response is the fall time, i.e.,
the time for the response to decrease from one value to another.
Fall time can be determined by measuring the time it takes for the
response to fall from its peak value to half its peak value, for
example, or the time it takes for the response to fall from ninety
percent of its peak value to ten percent of its peak value. The
signal decays more quickly in elevated [K.sup.+] environment and
more slowly in a normal [K.sup.+] environment, so the fall time in
the elevated [K.sup.+] environment is smaller than the fall time in
a normal [K.sup.+] environment. Processor 84 may detect the rate of
muscle relaxation with any analog or digital technique, such as
taking a difference at discrete points, measuring the time between
high and low values, or differentiating the response waveform.
It may be possible to observe the decline with a single stimulus.
Stimulus 136 evokes responses 138, 140. In addition to monitoring
fall time or slope as described above, processor 84 may detect the
pulse width or action potential duration of the response. Because
the response returns to resting more quickly in an elevated
[K.sup.+] environment than in a normal [K.sup.+] environment, the
pulse width of the in an elevated [K.sup.+] environment is narrower
than in a normal [K.sup.+] environment. The narrower pulse width is
associated with the shorter refractory period in an elevated
[K.sup.+] environment. Narrower pulse width in an elevated
[K.sup.+] environment has been demonstrated with both cardiac
muscle and skeletal muscle.
A set of stimuli 142 illustrates another distinction technique.
This process includes delivering pairs of stimuli separated by
different time intervals. In FIG. 4B, the initial pair of stimuli
is separated by a very short interval, and subsequent pairs are
separated by larger intervals. In an elevated [K.sup.+]
environment, the response will exhibit a two-peak ripple at a
smaller interval than in a normal [K.sup.+] environment. Processor
84 can detect the presence of the two-peak ripple using any signal
processing technique, including techniques mentioned above.
Another distinction technique is to "sweep" through a range of
frequencies, as illustrated by set of stimuli 148. In a normal
[K.sup.+] environment, the response 150 exhibits more rapid
summation and reaches a sustained response in a shorter time. In
contrast, the response 152 in an elevated [K.sup.+] environment is
slower to exhibit summation and sustained response. Processor 84
can detect the onset of rapid summation and sustained response any
signal processing technique, including techniques mentioned
above.
The signals depicted in FIGS. 4A and 4B are for purposes of
illustration and the invention is not limited to signals of this
type. Instead of measuring tension, as depicted in FIGS. 4A and 4B,
sensor 80 could respond to muscle motion or muscle length, for
example. In other embodiments, other signals may be measured in
other tissue, which may be sensitive to [K.sup.+] or other ion
concentrations. For example, action potentials may be measured in
nerve tissues.
As FIG. 4A shows, it may be more difficult to distinguish whether
[K.sup.+] is low or elevated when stimulations are applied at high
frequencies. Further, the frequency at which a normal [K.sup.+]
environment can be distinguished from an elevated [K.sup.+]
environment may vary from patient to patient. Accordingly, a
patient who has received IMD 12 may undergo one or more tests to
calibrate muscle response to [K.sup.+] or other tissue response to
[K.sup.+].
In other embodiments, the detection of different ion concentrations
may be performed in a similar manner. However, delivered stimuli
may be different depending on the tissue being stimulated and the
ion concentration being detected.
FIG. 5 illustrates an exemplary calibration procedure. Although
FIG. 5 illustrates an example embodiment related to monitoring
muscle tissue and [K.sup.+], the illustrated technique may be
applicable to calibration for monitoring of other tissues, such as
nerve tissue, which may be sensitive to [K.sup.+] and/or other ion
concentrations.
In a laboratory setting, while conditions are suitable for
stimulating the muscle and observing the response, IMD 12 delivers
one or more electrical stimulations to the muscle of the patient
via the electrodes (160). The stimulations may be delivered
according to a particular parameter, such as a known frequency. For
purposes of illustration, it is assumed that the stimulation
parameter is a known frequency of stimulation, and that the initial
known frequency is a low frequency. It is further assumed that the
characteristic of interest is whether the muscle exhibits a
sustained tissue response.
IMD 12 detects the response of the muscle to the stimulations (162)
and performs signal analysis to determine whether stimulations at
the known frequency produce a tissue response (164). If not, the
frequency may be changed (166), e.g., increased, and the testing
may be performed again (160). At some point, the patient will
exhibit a rippled response, and at a higher frequency the patient
will exhibit a sustained response.
At substantially the same time, the patient has his ECF [K.sup.+]
measured by conventional laboratory techniques. Data concerning
[K.sup.+] are then correlated to data pertaining to the patient's
response to stimulation at one or more frequencies. In one
embodiment, IMD 12 receives the data concerning measured [K.sup.+],
and processor 84 performs the correlation. In another embodiment,
another processor performs the correlation, and the relationship is
supplied to processor 84 via input/output element 88.
IMD 12 stores the relationship between a known [K.sup.+] and the
patient's response (168). In this way, a baseline measurement of
[K.sup.+] can be established for the patient. Future determinations
of [K.sup.+] can be measured against the baseline. If, at later
time, the patient exhibits a sustained response at lower frequency,
then [K.sup.+] has declined in comparison to the baseline.
Conversely, if the later patient exhibits a sustained response at
higher frequency, then [K.sup.+] has increased with respect to the
baseline.
Although FIG. 5 illustrates calibration by observing sustained
response, calibration may also be performed using other responses.
Other responses can include, for example, the rate of relaxation
following cessation of stimulation, the pulse width of a response,
the occurrence of summation in the response, the amplitude of a
response, or any combination thereof.
As part of the calibration, IMD 12 may deliver stimuli at different
amplitudes. By iterative experimentation, IMD 12 can discover what
amplitude of stimulation will produce a response. IMD 12 may be
programmed to adjust the amplitude of stimulation as appropriate.
Techniques to calibrate the IMD to detect other ions may be similar
to the described technique to calibrate IMD 12 for [K.sup.+].
FIG. 6 is a flow diagram illustrating a technique for monitoring
ECF potassium ion concentration and for delivering therapy in
response to a determination of ECF potassium ion concentration.
When, for example, processor 84 determines that it is time for a
scheduled monitoring or when processor 84 detects a triggering
event that can activate monitoring, processor 84 initiates the
monitoring process (170). Before actually conducting the
monitoring, however, processor 84 determines whether the conditions
are suitable for monitoring (172). An illustrative situation in
which conditions might not be suitable for monitoring is a
situation in which the patient has a high level of physical
activity. When a signal from an activity sensor indicates that the
patient is physically active, it may be difficult to monitor
[K.sup.+] accurately. When processor 84 determines that conditions
are not suitable for monitoring, processor 84 can defer monitoring
to a later time (174).
IMD 12 delivers one or more electrical stimulations to the tissue
of the patient (176). The stimulations may include a set of
stimulations delivered at a known frequency or a set of
stimulations that sweep through a range of frequencies. IMD 12
detects the response of the tissue to the stimulations (178).
Although not depicted in FIG. 6, stimulations and detection (176,
178) may be repeated. For example, a later set of stimulations may
be repeated at a known frequency that is different from an earlier
set of stimulations.
On the basis of the detections, processor 84 determines a
concentration of potassium ions in ECF of the patient (180). As
noted above, this determination can include determining an absolute
concentration, determining a relative concentration or determining
a change in concentration, or any combination thereof.
On the basis of the determination of a concentration of potassium
ions in ECF, processor 84 further determines whether action should
be taken. In the example FIG. 6, the action in question is whether
therapy is indicated (182). When therapy is indicated, processor 84
controls therapy element 90 to deliver therapy to the patient
(184). The invention is not limited to instances in which IMD 12
takes action in the form of administration of therapy. Other kinds
of action include transmitting a notification via input/output
element 88 or changing how often IMD 12 monitors [K.sup.+].
The results of the determination (180), and the delivery of
therapy, if any, may be recorded in memory 86 (186). Among other
purposes, data stored in memory are useful for monitoring the
change in [K.sup.+] over time and for documenting the response of
the patient to therapy. Although described above with respect to
[K.sup.+], the techniques illustrated by FIG. 6 may additionally or
alternative be used to monitor the concentration of ions other than
potassium.
EXAMPLE 1
FIG. 7 is a schematic diagram illustrating an experimental setup
that was used to test muscle contractions due to electrical
stimuli. As shown in FIG. 7, mouse skeletal muscle 202 was held
between clamps 208 and 210 in a chamber 190. Clamp 210 was
connected to a wall of chamber 190 by a support structure 206 while
clamp 208 was connected to force transducer 212. Force transducer
212 was connected to support structure 204, which was attached to
chamber 190. Chamber 190 was contained within bath 188. Electrical
stimulator 192 provided electrical stimuli to muscle 202 through
electrodes 198 and 200. Electrodes 198 and 200 were coupled to
electrical stimulator 192 by wires 194 and 196, respectively.
In the experiment described in FIGS. 7-9, bath 188 was set to 37
degrees Celsius, and chamber 190 was filled with potassium buffer
that was controlled to provide varying concentrations of potassium
ions to determine how muscle 202 contracts with electrical stimuli
in the presence of differing potassium ion concentrations. Muscle
202 was an isolated mouse skeletal muscle. Force transducer 212 was
a strain gauge. Biphasic electrical stimuli was delivered to muscle
202 via electrodes 198 and 200 in order to trigger isometric
contractions in the muscle. A computing device monitors the
measurements from force transducer 212 in real-time or offline. The
experimental setup described in FIG. 7 may be varied to determine
contraction forces from other tissues or using other devices.
FIG. 8 is a graph of experimental data showing muscle force in
various solutions of potassium versus time. Graph 214 shows
electrical stimuli 216 and 218 in conjunction with measured forces
of muscle 202 of FIG. 7. Broken line 220 represents contractions
when [K.sup.+] equals 2 millimoles (mM), solid line 222 represents
contractions when [K.sup.+] equals 4 mM, and dotted line 224
represents contractions when [K.sup.+] equals 10 mM. Contraction
force was highest when [K.sup.+] equaled 2 mM, which is a lower
[K.sup.+] than the normal potassium ion concentrations for a mouse.
A medium level of force was generated with electrical stimuli when
[K.sup.+] equaled 4 mM, and the lowest levels of force was
generated when [K.sup.+] equaled 10 mM. Normal [K.sup.+] of a mouse
is approximately 4 mM.
In the experiment, a burst electrical stimulation consisting of 5
pulses with a frequency of 50 Hz were applied to muscle 202. Pulses
were biphasic with anodic and cathodic pulse durations of 1
millisecond (ms), and 18 ms of pause between each pulse.
FIG. 9 is a graph of experimental data showing contraction
amplitude versus potassium concentration. Graph 226 displays
contraction amplitudes in Volts according to three different
electrical stimuli frequencies. Volts may be translated into force
measurements by a calibration procedure. Solid line 228 and
included closed boxes are representative of 50 Hz stimulation,
broken line 230 and included open boxes are representative of 100
Hz stimulation, and dotted line 232 and included closed circles are
representative of 150 Hz stimulation.
The [K.sup.+] was varied in the sequence of 4 mM, 10 mM, 4 mM, 2
mM, and 4 mM. The results showed that the amplitude of the force
generated by muscle 202 may be determined by the [K.sup.+] when the
stimulation frequency 50 Hz and 100 Hz. In addition, stimulation at
150 Hz may also be used to determine [K.sup.+] in skeletal muscle,
but was less sensitive to [K.sup.+] than the other frequencies
tested. Other frequencies not tested in the experiment of FIGS. 7-9
may also be useful for electrical stimulation.
In some embodiments, other tissues may be tested and may respond
similarly as the mouse skeletal muscle. Other frequencies and
[K.sup.+] may also be tested, while the exemplary conditions
provided herein are only a small sample of [K.sup.+] that may be
detected with electrical stimulation.
The invention may produce one of more advantages. In comparison
with conventional implantable ion sensors such as
electrochemistry-based ion sensors or optically based sensors, the
invention supports long-term implantation. Conventional ion sensors
have proven to be unstable over extended periods. Some sensors
require a periodic replacement of a sensing element, and other
sensors lose sensitivity when the body naturally encapsulates the
implanted elements. Some sensors also can be rejected by the body
of the patient.
IMDs such as those described above, however, have proven to be well
tolerated in the long term. Rejection rates are low. Further, the
IMD can respond to encapsulation by increasing the voltage of
stimulations to provoke a response.
The stimulations need not be painful. In practice, the patient may
very likely experience a tingle. The tingle may be uncomfortable,
but it would probably not be painful as long as stimulations are
adjusted to a voltage that provokes a response and is not
excessive. Further, as discussed above, the stimulations may be
therapeutic stimulation of, for example, cardiac muscle or nervous
tissue, that would have otherwise been delivered to the patient
whether or not [K.sup.+] was monitored. There may further be an
element of convenience to the patient, as the patient may reduce
the number of tests that rely upon blood samples.
IMDs such as those described above can be implanted using
conventional, well-established surgical techniques. In the case of
an IMD that delivers pacing or other heart therapies, an electrode
configured to deliver an electrical stimulation to a tissue may be
deployed as part of conventional device implantation technique,
with little or no additional incision or trauma to the patient.
Many patients experiencing heart failure may benefit from the
implantation of an IMD that combines pacing therapies and potassium
monitoring capability.
In addition, the invention supports embodiments that include one or
more external elements, which may offer further advantages. A
patient may receive the embodiment depicted in FIG. 1F, for
example, without surgery. An external electrode element, such as
that depicted in FIG. 1F, may be deployed at several sites on the
body of the patient without surgery. An external electrode element
may also be readily redeployed from one site to another.
Various embodiments of the invention have been described, but the
invention is not limited to these particular embodiments. Although
the invention has been depicted in the context of a pacemaker
having one or more leads configured to deliver pacing stimuli to a
heart, the invention can also be implemented in conjunction with
other implantable and external devices. The invention can be
implemented with a neurostimulator that includes a lead configured
to deliver a pacing stimulation to a nerve, or a drug pump that
includes a pump configured to deliver a drug to the patient from a
reservoir. The invention may also be implemented as a standalone
ion imbalance detector.
The invention may be embodied in a computer-readable medium with
instructions that cause a programmable processor to carry out the
techniques described above. A "computer-readable medium" includes
but is not limited to read-only memory, Flash memory, EPROM and a
magnetic or optical storage medium. The medium may comprise
instructions for causing a programmable processor to control a
pulse generator to deliver an electrical stimulation to a muscle in
a patient, for example, or receive from a sensor a signal
indicative of a response of the tissue to the electrical
stimulations.
Further, although described above primarily with reference to
skeletal muscle tissue and potassium ion concentrations, the
techniques of the invention may be applied to monitoring the
response of any tissue to the concentration of any one or more
ions. Example tissues include skeletal, cardiac or smooth muscle,
as well and nerve or dermal tissues. Example ions include
potassium, sodium, chloride, calcium, or magnesium ions, as well as
drugs that become ions in the blood or ECF, small molecules, or
endogenously charged molecules. Examples of drugs that may be
monitored as ions in the ECF include lodipine, felodipine,
furosemide, bumetanide, isosorbide dinitrate, dantrolene, digoxin,
digitalis, carisoprodol, chlorphenesin, calcium channel blockers,
diuretics, vasodilators, muscle relaxants and calcium blocker for
malignant hyperthermia. These and other embodiments are within the
scope of the following claims.
* * * * *